Evaluation of LL-37 in healing of hard-to-heal venous leg ulcers: A multicentric prospective randomized placebo-controlled clinical trial.

Many patients with venous leg ulcers do not reach complete healing with compression treatment alone, which is current standard care. This clinical trial HEAL LL-37 was a phase IIb double-blind, randomized, placebo-controlled study, with the aim to evaluate the efficacy and safety of a new drug LL-37 for topical administration, in combination with compression therapy, in 148 patients suffering from hard-to-heal venous leg ulcers. The study had three arms, consisting of two groups treated with LL-37 at concentrations of 0.5 or 1.6 mg/mL, and a placebo cohort. Patients had a mean age of 67.6 years, a median ulcer duration of 20.3 months, and a mean wound size at the time of randomization of 11.6 cm2 . Efficacy analysis performed on the full study population did not identify any significant improvement in healing in patients treated with LL-37 as compared with the placebo. In contrast, a post hoc analysis revealed statistically significant improvement with LL-37 treatment in several interrelated healing parameters in the subgroup of patients with large target wounds (a wound area of at least 10 cm2 at randomization), which is a known negative prognostic factor for healing. The study drug was well tolerated and safe in both dose strengths. In summary, this clinical trial did not detect any significant differences in healing of venous lower leg ulcers in the entire study cohort comparing patients treated with LL-37 versus placebo. A subgroup analysis provided an interesting observation that LL-37 could offer a treatment benefit in patients with large ulcers, exigently warranting a further study adequately powered to statistically assess the treatment outcome in this patient group.

[The quantitative evaluation of the serum acute phase proteins (APP) of patients undergoing a curative resection for non-small cell lung cancer (NSCLC)]. / Ocena zmian ilosciowych bialek ostrej fazy w surowicy krwi chorych poddanych radykalnej resekcji niedrobnokomórkowego raka pluca.

The aim of this study was to quantitatively evaluate serum APP in patients undergoing the radical resection for NSCLC. The quantitative changes in APP were correlated with the cancer type, clinical staging and grading and the procedure type. Also, the impact of selected post-operative complications on the APP serum concentrations was evaluated. 46 patients undergoing surgery secondary to NSCLC in the years 2003-2004 were analyzed. The patients' age varied from 45 to 77 years with an average of 61.1. The most common pathological cancer type was the squamous cell cancer (24 patients) and adenocarcinoma (17 patients). The majority of the patients were stage IIB (15 patients) and IIIA (14 patients). The following APPs were evaluated in the patients' serum by Laurell rocket immunoelectrophoresis: C-reactive Protein (CRP), alfa-1 antichymotrypsine (alfa-1 ACT), alfa-1 antitrypsine (AT), alfa-2 macroglobuline (alfa2 M), ceruloplasmin (Cp), haptoglobine (Hp) and transferrin (Tf). Significantly higher serum AT level were found in patients with adenocarcinoma as compared to other pathology types. Patients with the squamous cell cancer had a significantly higher level of alfa-2 M and Cp. There was no significant difference in APP levels between the cancer grading types. In the group of patients with T3 or T4 stage the following five APPs were significantly elevated: CRP, AGP, alfa-1 ACT, alfa-2 M and Cp. Patients with regional lymph nodes metastasis (N2 or N2) had significantly higher level of AT, CRP and Hp. Patients undergoing more significant procedures (pneumonectomy, prolonged procedure time) and those with morbidities (rethoracotomy, blood transfusions) showed significantly higher levels of alfa-1 ACT, AGP and Cp. The most common post-operative complications were prolonged air-leak requiring probronchoscopy. In both complications a significantly higher level of AGP was observed. Patients with adenocarcinoma of the lung and regional lymph node metastasis have significantly higher serum levels of AT. This protein could be considered as one of the indicators of cancer involvement and could be a marker of the cancer recurrence. AGP is a protein that correlates positively with a more advanced clinical stage, and the extent of the surgical procedure as well as with the higher risk of morbidity. This could serve as a marker of higher post-operative complication rate.